Dry granulation is a process in which granulates are formed by a compaction step that is followed by sizing the compacts into particles that can be processed easily. It is often used to improve flow properties and/or densify the formulation which can facilitate further manufacturing processes such as tableting, encapsulation and powder filling. The compacts are made directly from powder blends that usually contain an active ingredient and other excipients including a lubricant.
Pharmaceutical manufacturers prefer the use of dry granulation techniques to wet granulation methods because of shorter processing times and cost advantages. However, dry granulation is generally limited to those situations in which the drug or active ingredient has physical characteristics suitable for forming pharmaceutically acceptable granulations and dosage forms such as tablets.
The addition of at least one excipient to the formulation is generally required and will contribute to increasing the tablet size of the final product. As tablet size must be within certain parameters to function as a suitable dosage form, there is a limit beyond which increasing tablet size to accommodate increasing amounts of excipients to enhance compactability is not practical. As a result, manufacturers are often limited to using the dry granulation method for formulations containing a low dose of the active ingredient per compressed tablet such that the formulation may accommodate sufficient levels of excipient to make dry granulation practical.
In the development of pharmaceutical dosage forms, it is important to balance several different objectives. It is important to prepare a pharmaceutical dosage form as economically as possible. It would be desirable to have a simple production method comprising a few processing steps. The dosage form should also optimally make available the active compound contained therein to the patient. Further, the dosage form should be easy to swallow. Smaller dosage forms are better accepted by patients and increase patient compliance.
Tablets are typically formed by pressure being applied to the material to be tableted on a tablet press. A formulation must have good flow properties for precise volumetric feeding of the material to the die cavity and suitable compressibility, compactability, and ejection properties to form a tablet.
There are a number of tablet presses, each varying in productivity but similar in basic function and operation. All compress a tablet formulation within a die cavity by pressure exerted between two steel punches, a lower punch and an upper punch. Tablet presses are typically designed to have a hopper for holding and feeding the formulation, a feeding mechanism for feeding the formulation to the die cavity, provision for placement of punches and dies, and in rotary tablet presses a cam track for guiding the movement of the punches. Two types of tablet presses are the single station or single-punch press and the multistation rotary press. Some tablet presses provide longer dwell times than others, allowing increased bonding to occur. Other presses may provide precompression.
Azithromycin, which is also named 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A, generally, is not considered to be amenable to the production of directly compressible tablets of azithromycin formulations.
It would be desirable to develop an azithromycin formulation that is amenable to form suitable granules by dry granulation methods or to form tablets, from these granules, that have acceptable hardness and friability.